This is a proposal by the Department of Chemistry of the University of Colorado to acquire a diffractometer for macromolecular x-ray crystallography. Representative research programs which would benefit immediately, including intramural and extramural investigators, fall into three major areas: (i) molecular mechanisms of bacterial pathogenesis, exemplified by crystallographic work on the exotoxins of Pseudomonas aeruginosa and Bacillus anthracis; (ii) mechanisms of regulation of gene expression at the level of translation, represented by crystallographic work on the single strand DNA binding protein of bacteriophage T4; and (iii) mechanism of RNA catalysis.